Advanced CancerPhase 1NCT02407990
Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors
A Phase 1 study testing BGB-A317 in people with Advanced Cancer, run by BeiGene at 27 sites in 5 countries.
Trial summary
This study evaluated the safety, tolerability, pharmacokinetic profile and treatment effect of a new drug known as BGB-A317 in participants with advanced tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- BGB-A317
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 451 participants
- Where
- 27 sitesin 5 countries
- Study dates
- 2 Jun 2015to 12 Aug 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have had a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy was available.
- For Phase 1A: no specific restriction
- For Phase 1B: histology specified below:
- non-small cell lung cancer (participants with documented epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement should have been excluded) ii. ovarian cancer iii. gastric cancer iv. hepatocellular carcinoma (HCC, Barcelona-Clinic Liver Cancer stage C, stage B not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach, and Child-Pugh A) v. head and neck squamous cell carcinoma vi. esophageal carcinoma vii. triple negative breast cancer viii. cholangiocarcinoma ix. renal cell cancer, bladder cancer, melanoma, Merkel-cell carcinoma, sarcoma, gastrointestinal stromal tumor, or cutaneous squamous cell carcinoma. Or any other solid tumors with known microsatellite instability-high or mismatch repair deficient status, such as colorectal cancer or pancreatic cancer
- Participants with previously treated brain metastasis (es) that were asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment were permitted.
- Participants must have had archival tumor tissues or agreed to a tumor biopsy for analysis of predictive biomarkers such as programmed death-ligand 1 (PD-L1). (Fresh tumor biopsies were strongly recommended at baseline for biomarker analysis in participants with readily accessible tumor lesions and who consented to the biopsies).
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- Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1.
- Eastern Cooperative Oncology Group performance status of ≤ 1.
- Participants must have had adequate organ function as indicated by the following laboratory values:
- Absolute neutrophil count ≥ 1,500 /microliter
- Platelets ≥ 100,000 / milliliter (mL)
- Hemoglobin ≥ 9 grams/deciliter or ≥ 5.6 millimoles/liter
- Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
- Serum total bilirubin ≤ 1.5 X ULN
- Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X ULN or ≤ 5 X ULN for participants with liver metastases
- International normalized ratio or prothrombin time ≤ 1.5 X ULN
- Activated partial thromboplastin time ≤ 1.5 X ULN
Who cannot join
- History of severe hypersensitivity reactions to other Monoclonal antibodies.
- Prior malignancy active within the previous 2 years except for tumor for which a participant was enrolled in the study, and locally curable cancers that had been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
- Prior therapies targeting PD-1 or PD-L1.
- Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.
- Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded.
- Participants should have been excluded if they had a condition requiring systemic treatment with either corticosteroids (> 10 milligrams daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
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- Had history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
- Known history of human immunodeficiency virus.
- Active infection requiring therapy, positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid except in participant with HCC, who met the following criteria:
- Hepatitis B virus (HBV) viral load < 200 international units/mL (approximately 1000 combined positive score/mL)
- Participants with active HBV infection needed to be on anti-HBV suppression ≥ 3 months, throughout treatment and for 6 months after
- Participants hepatitis C virus (HCV)-positive after successful treatment (defined as sustained virologic response [SVR] 12 or SVR 24) were allowed as long as 4 weeks had passed between completion of HCV therapy and start of study drug
- Use of any vaccines against infectious diseases (for example, influenza, varicella) within 4 weeks (28 days) of initiation of study therapy and 60 days after the last administration of the study medication.
- Note: Other protocol defined Inclusion/Exclusion criteria may have applied.
Trial locations and contacts
27 sites in 5 countries.
27 sites in 5 countries
Australia13 sites
Royal Adelaide Hospital
Adelaide, South Australia
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Monash Health
Clayton, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria
Austin Health Hospital
Heidelberg, Victoria
Cabrini Hospital
Malvern, Victoria, 3144
Nucleus Network
Melbourne, Victoria, 3004
Royal Melbourne Hospital
Melbourne, Victoria
Linear Clinical Research/Sir Charles Gairdner Hospital
Nedlands, Western Australia
Tasman Oncology Research Ltd
Southport, Queensland, 4216
Prince of Wales Hospital
Sydney, New South Wales
The Queen Elizabeth Hospital
Woodville South, South Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Taiwan6 sites
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301
National Cheng Kung University Hospital
Tainan, 704
Taipei Veterans General Hospital
Taipei, 11217
National Taiwan University Hospital
Taipei
Linkou Chang Gung Memorial Hospital
Taoyuan, 33305
Chang Gung Memorial Hospital, Sachin
Taoyuan, 61363
New Zealand3 sites
Auckland City Hospital
Grafton, 1023
Waikato
Hamilton, 3204
Wellington Hospital
Wellington, 6022
South Korea3 sites
Seoul National University Bundang Hospital
Seongnam, Kyeonggi-do, 13620
Seoul National University Hospital
Seoul, 3080
Asan Medical Center
Seoul, 5505
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Oncology Consultants, P.A.
Houston, Texas, 77024-2545
About this study
Official title: A Phase 1A/1B, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Subjects With Advanced Tumors
This study evaluated the safety, tolerability, pharmacokinetic profile and treatment effect of a new drug known as BGB-A317 in participants with advanced tumors.
- Conditions
- Advanced Cancer
- Being tested
- BGB-A317
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BGB-A317Biological
In the dose escalation part, the dose levels were escalated following a modified 3+3 dose escalation scheme. In the scheduled exploration part, participants were assigned to doses and dose schedules. In the fixed dose exploration part, participants were assigned to dose group(s) not to exceed the maximum tolerated dose. In the dose expansion part, participants were assigned to different groups based on their tumor type.
BGB-A317Biological
Participants were assigned to different groups based on their tumor types
| Study group | Role | What they receive |
|---|---|---|
| BGB-A317 Phase 1A | Experimental | Not described Receives: Biological: BGB-A317 |
| BGB-A317 Phase 1B | Experimental | Not described Receives: Biological: BGB-A317 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1A: Number of Participants Experiencing Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version [v] 4.03 2010).
Measured: Day -28 through 5 years and 2 months
Phase 1A: Number Of Participants With Abnormal Physical Examination Values
A complete physical examination, vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1A. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required.
Measured: Day 1 and Day 15 of each cycle through 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography [or equivalent diagnostic test]) were performed at pre-specified time points for Phase 1A. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment.
Measured: Day 15 of cycle 1, Day 1 of Cycle 2 and all additional cycles, and 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Phase 1A: Number Of Participants With Abnormal Electrocardiograms
Electrocardiograms were obtained at pre-specified time points. Significant QT interval corrected for heart rate (QTc) prolongation was defined as an interval ≥ 500 milliseconds (msec) or an interval which increases by ≥ 60 msec over baseline.
Measured: Days 1 and 15 of cycle 1; Day 1 of cycle 2 and all additional cycles; Day 1 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Phase 1A: Number Of Participants With Abnormal Laboratory Values
Clinical chemistry, hematology, coagulation, and urinalysis were performed at pre-specified time points for Phase 1A. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported.
Measured: Day -28 (predose), Days 1, 8, and 15 of cycle 1; Days 1 and 15 of cycle 2 and additional cycles; Days 1 and 15 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Phase 1A: Number Of Participants Experiencing Severe AEs
All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and serious adverse event (SAE) recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe.
Measured: Day -28 through 5 years and 2 months
Phase 1B: Objective Response Rate (ORR)
The ORR was defined as the percentage of participants in the study whose best overall response was either complete response (CR) or partial response (PR) as assessed by investigators based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.
Measured: Day -28 through 5 years and 2 months
Secondary outcomes (23)
Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab
Measured: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab
Measured: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab
Measured: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A: Half-life (T½) For Tislelizumab
Measured: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A - Part 3: Clearance (Cl) For Tislelizumab
Measured: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs)
Immunogenicity was summarized by the number and percentage of participants who developed detectable treatment-emergent ADAs, which included positive ADAs and neutralizing antibodies (NAb).
Measured: Day 1 of Cycles 1 through 15
Phase 1A: ORR
The ORR was defined as the percentage of participants in the study whose best overall response was either CR or PR as assessed by investigators based on RECIST v 1.1.
Measured: Day -28 through 5 years and 2 months
Phase 1A: CR Rate
The CR rate was based on RECIST v 1.1 and the results of Investigator evaluations.
Measured: Day -28 through 5 years and 2 months
Phase 1A: PR Rate
The PR rate was based on RECIST v 1.1 and the results of Investigator evaluations.
Measured: Day -28 through 5 years and 2 months
Phase 1A: Stable Disease (SD) Rate
The SD rate was based on RECIST v 1.1 and the results of Investigator evaluations.
Measured: Day -28 through 5 years and 2 months
Phase 1A: Progression-free Survival (PFS)
PFS was defined as the time from the date of first study dose to disease progression or death whichever occurs first. Participants without an event (no disease progression or death) were censored at the date of "last tumor assessment". Participants with no baseline or post-baseline tumor assessments were censored at Day 1. PFS was based on RECIST v 1.1 and the results of Investigator evaluations.
Measured: Day -28 through 5 years and 2 months
Phase 1A: Overall Survival (OS)
OS was defined as the time interval between the date of the first study drug dose to the date of death for any cause. Kaplan-Meier methodology was used to estimate OS at various time points. The OS was based on RECIST v 1.1 and the results of Investigator evaluations.
Measured: Day -28 through 5 years and 2 months
Phase 1A: Duration Of Response (DOR)
DOR for responders (CR or PR) was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurred earlier. For participants who were alive without progression following the qualifying response, DOR was censored on the date of last evaluable tumor assessment or last follow-up for progression of disease. The DOR was based on RECIST v 1.1 and the results of Investigator evaluations.
Measured: Day -28 through 5 years and 2 months
Phase 1B: Number of Participants Experiencing AEs
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the NCI-CTCAE (v 4.03 2010).
Measured: Day -28 through 5 years and 2 months
Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab
Measured: Pre-dose, Day 1 Cycle 5 and every other Cycle in the first 6 months, every 4 cycles in the next 6 months, once every 6 months up to end of treatment (up to 5 years and 2 months)
Phase 1B: PFS
PFS was defined as the time from the date of first study dose to disease progression or death whichever occurs first. Participants without an event (no disease progression or death) were censored at the date of "last tumor assessment". Participants with no baseline or post-baseline tumor assessments were censored at Day 1. PFS was based on RECIST v 1.1 and the results of Investigator evaluations.
Measured: Day -28 through 5 years and 2 months
Phase 1B: Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who achieve CR, PR, and SD based on RECIST v 1.1 in participants with select tumor types.
Measured: Day -28 through 5 years and 2 months
Phase 1B: Clinical Benefit Rate (CBR)
The CBR was defined as the percentage of participants who achieved CR, PR, and durable SD [SD ≥24 weeks] based on RECIST v 1.1 in participants with select tumor types.
Measured: Day -28 through 5 years and 2 months
Phase 1B: Number Of Participants With Abnormal Physical Examination Values
A complete physical examination, vital signs (SBP, DBP, pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1B. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required.
Measured: Day -28 (predose), Days 1, 4, 8, and 15 of cycle 1; Day 1 of cycle 2; through 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography [or equivalent diagnostic test]) were performed at pre-specified time points for Phase 1B. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment.
Measured: Day -28 (predose), Day 1 of cycle 2 and additional cycles, and 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants With Abnormal Electrocardiograms
Electrocardiograms were obtained at pre-specified time points. Significant QTc prolongation was defined as an interval ≥ 500 msec or an interval which increases by ≥ 60 msec over baseline.
Measured: Day -28 (predose), Days 1 and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants With Abnormal Laboratory Values
Clinical chemistry, hematology, coagulation, and urinalysis will be performed at pre-specified time points for Phase 1A and Phase 1B respectively. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported.
Measured: Day -28 (predose), Days 1, 8, and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants Experiencing Severe AEs
All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and SAE recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe.
Measured: Day -28 through 5 years and 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2015 (estimated)
- Study start2 Jun 2015
- Primary completion12 Aug 2020
- Study completion12 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 451 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Principal investigator, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02407990
- Sponsor's protocol ID
- BGB-A317_Study_001
- Status last verified
- Oct 2021
- First submitted
- 26 Mar 2015
- Last updated
- 17 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Desai J, Deva S, Lee JS, Lin CC, Yen CJ, Chao Y, Keam B, Jameson M, Hou MM, Kang YK, Markman B, Lu CH, Rau KM, Lee KH, Horvath L, Friedlander M, Hill A, Sandhu S, Barlow P, Wu CY, Zhang Y, Liang L, Wu J, Paton V, Millward M. Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. J Immunother Cancer. 2020 Jun;8(1):e000453. doi: 10.1136/jitc-2019-000453.
PubMed 32540858Ye D, Desai J, Shi J, Liu SM, Shen W, Liu T, Shi Y, Wang D, Liang L, Yang S, Ma X, Jin W, Zhang P, Huang R, Shen Z, Zhang Y, Wu YL. Co-enrichment of CD8-positive T cells and macrophages is associated with clinical benefit of tislelizumab in solid tumors. Biomark Res. 2023 Mar 7;11(1):25. doi: 10.1186/s40364-023-00465-w.
PubMed 36879284
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1A/1B, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Subjects With Advanced Tumors
- ClinicalTrials.gov ID
- NCT02407990
- Acronym / sponsor ID
- BGB-A317_Study_001
- Conditions
- Advanced Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 451 participants (actual)
- Lead sponsor
- BeiGeneIndustry (pharma, biotech, devices)
- Study start
- 2 Jun 2015 (actual)
- Primary completion
- 12 Aug 2020 (actual)
- Study completion
- 12 Aug 2020 (actual)
- First posted
- 3 Apr 2015 (estimated)
- Results
- Posted 17 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated the safety, tolerability, pharmacokinetic profile and treatment effect of a new drug known as BGB-A317 in participants with advanced tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BGB-A317 Phase 1A | Experimental | Biological: BGB-A317 |
| BGB-A317 Phase 1B | Experimental | Biological: BGB-A317 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Participants must have had a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy was available.
- Participants with previously treated brain metastasis (es) that were asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment were permitted.
- Participants must have had archival tumor tissues or agreed to a tumor biopsy for analysis of predictive biomarkers such as programmed death-ligand 1 (PD-L1). (Fresh tumor biopsies were strongly recommended at baseline for biomarker analysis in participants with readily accessible tumor lesions and who consented to the biopsies).
- Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1.
- Eastern Cooperative Oncology Group performance status of ≤ 1.
Key exclusion criteria (14 listed)
- History of severe hypersensitivity reactions to other Monoclonal antibodies.
- Prior malignancy active within the previous 2 years except for tumor for which a participant was enrolled in the study, and locally curable cancers that had been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
- Prior therapies targeting PD-1 or PD-L1.
- Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.
- Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BGB-A317In the dose escalation part, the dose levels were escalated following a modified 3+3 dose escalation scheme. In the scheduled exploration part, participants were assigned to doses and dose schedules. In the fixed dose exploration part, participants were assigned to dose group(s) not to exceed the maximum tolerated dose. In the dose expansion part, participants were assigned to different groups based on their tumor type. | Biological | BGB-A317 Phase 1A |
| BGB-A317Participants were assigned to different groups based on their tumor types | Biological | BGB-A317 Phase 1B |
Primary outcome
Phase 1A: Number of Participants Experiencing Adverse Events (AEs)
Time frame: Day -28 through 5 years and 2 months
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of an investigational product. All AEs were monitored per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version [v] 4.03 2010).
Phase 1A: Number Of Participants With Abnormal Physical Examination Values
Time frame: Day 1 and Day 15 of each cycle through 30 (+/- 7) days after last dose (up to 5 years and 2 months)
A complete physical examination, vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, temperature, and respiratory rate), and weight were performed pre-specified time points for Phase 1A. During the treatment period, symptom-directed physical examinations were performed. If there were no complaints and no abnormal findings from the previous visit for a particular organ system, a physical examination of that organ system was not required.
Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Time frame: Day 15 of cycle 1, Day 1 of Cycle 2 and all additional cycles, and 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Ophthalmological examinations (such as eyesight/visual acuity, fundoscopy, slit lamp microscopy, and optical coherence tomography [or equivalent diagnostic test]) were performed at pre-specified time points for Phase 1A. Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) will be assessed by an appropriate specialist at Screening. Participants dosed underwent subsequent ophthalmologic examinations, a specified in the protocol, by an appropriate specialist during study treatment.
Phase 1A: Number Of Participants With Abnormal Electrocardiograms
Time frame: Days 1 and 15 of cycle 1; Day 1 of cycle 2 and all additional cycles; Day 1 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Electrocardiograms were obtained at pre-specified time points. Significant QT interval corrected for heart rate (QTc) prolongation was defined as an interval ≥ 500 milliseconds (msec) or an interval which increases by ≥ 60 msec over baseline.
Phase 1A: Number Of Participants With Abnormal Laboratory Values
Time frame: Day -28 (predose), Days 1, 8, and 15 of cycle 1; Days 1 and 15 of cycle 2 and additional cycles; Days 1 and 15 of cycle 4; 30 (+/- 7) days after last dose (up to 5 years and 2 months)
Clinical chemistry, hematology, coagulation, and urinalysis were performed at pre-specified time points for Phase 1A. If warranted, additional testing was done, or the relevant tests done more frequently in accordance with institutional guidelines. All participants who had any Grade 3 or Grade 4 laboratory abnormalities at withdrawal from the study were followed up until they had returned to Grade 1 or Grade 2, unless these were not likely to improve due to the underlying disease. Participants experiencing decreases (low) and increases (high) to ≥ Grade 3 are reported.
Phase 1A: Number Of Participants Experiencing Severe AEs
Time frame: Day -28 through 5 years and 2 months
All AEs were monitored per the NCI-CTCAE (v 4.03 2010). In addition to performing the CTCAE assessment, the intensity of each AE and serious adverse event (SAE) recorded was assigned to one of the following categories based on the Investigator's clinical judgment: Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate: An event that is sufficiently discomforting to interfere with normal everyday activities; severe: An event that prevents normal everyday activities. Severity was a category utilized for rating the intensity of an event and, accordingly, both AEs and SAEs could be assessed as severe.
Phase 1B: Objective Response Rate (ORR)
Time frame: Day -28 through 5 years and 2 months
The ORR was defined as the percentage of participants in the study whose best overall response was either complete response (CR) or partial response (PR) as assessed by investigators based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.
23 secondary outcomes
Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A: Half-life (T½) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A - Part 3: Clearance (Cl) For Tislelizumab
Time frame: Cycle 1 Day 1-1 hour pre-dose, End of infusion, 1, 5, 6, 24, and 72 hours post-dose; Day 15 and Cycle 2 Day 1 Pre-dose
Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs)
Time frame: Day 1 of Cycles 1 through 15
Phase 1A: ORR
Time frame: Day -28 through 5 years and 2 months
Phase 1A: CR Rate
Time frame: Day -28 through 5 years and 2 months
Phase 1A: PR Rate
Time frame: Day -28 through 5 years and 2 months
Phase 1A: Stable Disease (SD) Rate
Time frame: Day -28 through 5 years and 2 months
Phase 1A: Progression-free Survival (PFS)
Time frame: Day -28 through 5 years and 2 months
Phase 1A: Overall Survival (OS)
Time frame: Day -28 through 5 years and 2 months
Phase 1A: Duration Of Response (DOR)
Time frame: Day -28 through 5 years and 2 months
Phase 1B: Number of Participants Experiencing AEs
Time frame: Day -28 through 5 years and 2 months
Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab
Time frame: Pre-dose, Day 1 Cycle 5 and every other Cycle in the first 6 months, every 4 cycles in the next 6 months, once every 6 months up to end of treatment (up to 5 years and 2 months)
Phase 1B: PFS
Time frame: Day -28 through 5 years and 2 months
Phase 1B: Disease Control Rate (DCR)
Time frame: Day -28 through 5 years and 2 months
Phase 1B: Clinical Benefit Rate (CBR)
Time frame: Day -28 through 5 years and 2 months
Phase 1B: Number Of Participants With Abnormal Physical Examination Values
Time frame: Day -28 (predose), Days 1, 4, 8, and 15 of cycle 1; Day 1 of cycle 2; through 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings
Time frame: Day -28 (predose), Day 1 of cycle 2 and additional cycles, and 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants With Abnormal Electrocardiograms
Time frame: Day -28 (predose), Days 1 and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants With Abnormal Laboratory Values
Time frame: Day -28 (predose), Days 1, 8, and 15 of cycle 1; Day 1 of cycle 2 and additional cycles; 30 (+/- 7) days after last dose up to 5 years and 2 months
Phase 1B: Number Of Participants Experiencing Severe AEs
Time frame: Day -28 through 5 years and 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32540858Desai J, Deva S, Lee JS, Lin CC, Yen CJ, Chao Y, Keam B, Jameson M, Hou MM, Kang YK, Markman B, Lu CH, Rau KM, Lee KH, Horvath L, Friedlander M, Hill A, Sandhu S, Barlow P, Wu CY, Zhang Y, Liang L, Wu J, Paton V, Millward M. Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. J Immunother Cancer. 2020 Jun;8(1):e000453. doi: 10.1136/jitc-2019-000453.
- Derived from this study: PubMed 36879284Ye D, Desai J, Shi J, Liu SM, Shen W, Liu T, Shi Y, Wang D, Liang L, Yang S, Ma X, Jin W, Zhang P, Huang R, Shen Z, Zhang Y, Wu YL. Co-enrichment of CD8-positive T cells and macrophages is associated with clinical benefit of tislelizumab in solid tumors. Biomark Res. 2023 Mar 7;11(1):25. doi: 10.1186/s40364-023-00465-w.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director principal investigator
BeiGene
27 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BGB-A317 in people with Advanced Cancer, run by BeiGene at 27 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in Australia, Taiwan, New Zealand, South Korea, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1A: Number of Participants Experiencing Adverse Events (AEs) (time frame: Day -28 through 5 years and 2 months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02407990, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2021.